title: The in vitro anti-tumor efficacy and the pharmacokinetics of N3-o-toluyl-fluorouracil loaded nanosuspension (TFu-LNS).
abstract: N3-o-toluyl-fluorouracil (TFu) was a potent water-insoluble prodrug of 5-fuorouracil (5-Fu). To improve the solubility of TFu, TFu loaded nanosuspension (TFu-LNS) was prepared by high-pressure homogenization method. The results of in vitro release studies showed that 5-Fu was sustained released from TFu-LNS. Then in vitro antitumor activity of TFu-LNS in terms of antiproliferative activity, induction of apoptosis and G1 cycle arrest on human breast adenocarcinoma cell line (MCF-7) and human gastric carcinoma cell line (BGC) was evaluated. The results of MTT assay showed that TFu-LNS exhibited higher antiproliferative activity against MCF-7 and BGC cells than TFu DMSO-water solution and 5-Fu solution. The apoptosis induced by TFu-LNS was assessed by Annexin V-FITC/PI double staining and Tunnel assay. And the results of two methods both clearly indicated that the superiority of TFu-LNS to TFu DMSO-water solution and 5-Fu solution in increasing the apoptosis rate of MCF-7 and BGC cells. The results of flow cytometric (FCM) analysis demonstrated that TFu-LNS could induce G1 cycle arrest of MCF-7 and BGC cells. Furthermore, in vivo pharmacokinetics study in Wistar rats indicated that TFu-LNS was capable of increasing the parameters of AUC(0-infinity) and MRT significantly by sustained releasing 5-Fu. Therefore, the overall results suggested that the TFu-LNS could enhance anti-tumor effect and hold great potential to be developed for cancer treatments.
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Shandong University, 44 Wenhua Xilu, Jinan 250012, China.
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.forename: Juan
authors.initials: J
authors.lastname: Zhang
authors.forename: Lixia
authors.initials: L
authors.lastname: Feng
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Na
authors.initials: N
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D008422:Materials Testing; D051379:Mice; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism; D049329:Nanostructures / Q000008:administration & dosage / Q000737:chemistry; D011355:Prodrugs / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013535:Suspensions; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; C517181:N3-o-toluyl-fluorouracil; D011355:Prodrugs; D013535:Suspensions; D005472:Fluorouracil